Hemangiomas are the most common tumor of infancy, with a prevalence of 5-10% at one year of age. We recently discovered a previously unrecognized association between hypothyroidism and infantile hemangiomas, due to the expression of type 3 iodothyronine deiodinase (D3) in these tumors. This research grew out of our clinical observations of an infant seen in the first year of my endocrinology fellowship. D3 is a selenoenzyme normally present in the brain and placenta as the physiologic inactivator of thyroxine and triiodothyronine. Extremely high levels of D3 activity are present in proliferative hemangioma tissue, causing the rapid inactivation of thyroid hormone. In the case of children with high tumor burden, severe hypothyroidism can develop due to the inability of the infant's thyroid to secrete hormone faster than it is inactivated by the tumor. Since the publication of these findings, several additional children have been diagnosed and three other institutions have published reports of infants with hepatic hemangiomas and acquired hypothyroidism. We have termed this condition "consumptive hypothyroidism." The goals of this proposal are to determine the clinical consequences of D3 expression in hemangiomas and characterize the molecular mechanism(s) for its expression. The large population of hemangioma patients seen by the Vascular Anomalies Center of Children's Hospital Boston will be studied prospectively to determine the incidence of this endocrinopathy and the optimal means of treating their thyroid dysfunction. Patient specimens will be analyzed by immunohistochemistry using two newly generated D3 antibodies. Human endothelial cells have been successfully cultured from surgical specimens and will be used as a model to study the transcription regulation of D3. Under the mentorship of Dr. P. Reed Larsen, the candidate will receive training in molecular biology and clinical thyroidology with the goal of becoming an independent investigator and an expert in the management of pediatric thyroid disease.